A G1 Checkpoint Mediated by the Retinoblastoma Protein That is Dispensable in Terminal Differentiation but Essential for Senescence

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2009 Dec 17

PMID 20008551

Citations 33

Authors

Srikanth Talluri

Christian E Isaac

Mohammad Ahmad

Shauna A Henley

Sarah M Francis

Alison L Martens

Rod Bremner

Frederick A Dick

Affiliations

Soon will be listed here.

Abstract

Terminally differentiated cell types are needed to live and function in a postmitotic state for a lifetime. Cellular senescence is another type of permanent arrest that blocks the proliferation of cells in response to genotoxic stress. Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA replication in senescence that is distinct from its role in permanent cell cycle exit associated with terminal differentiation. Our work demonstrates that a subtle mutation in pRB that cripples its ability to interact with chromatin regulators impairs heterochromatinization and repression of E2F-responsive promoters during senescence. In contrast, terminally differentiated nerve and muscle cells bearing the same mutation fully exit the cell cycle and block E2F-responsive gene expression by a different mechanism. Remarkably, this reveals that pRB recruits chromatin regulators primarily to engage a stress-responsive G(1) arrest program.

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